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GENE EXPRESSION ANALYSIS OF DENDRITIC/LANGERHANS CELLS AND LANGERHANS CELL HISTIOCYTOSIS.

Rust1, R., Kluiver1, J., Visser1, L., Harms1, G., Blokzijl1, T., Kamps2, W., Poppema1, S., and van den Berg1, A. 1Department of Pathology and Laboratory Medicine, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands. 2Department of Pediatric Oncology, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands.
Abstract

This study by researchers in the departments of Pathology and Laboratory Medicine, and Pediatric Oncology at the University of Groningen demonstrated that MatTek’s Human Langerhans/Dendritic Cells are an excellent in vitro model for studying the gene expression of Langerhans cell histiocytosis (LCH). Langerhans cell histiocytosis (LCH) is a neoplastic disorder that results in clonal proliferation of cells with a Langerhans cell (LC) phenotype. The pathogenesis of LCH is still poorly understood. In the present study, serial analysis of gene expression (SAGE) was applied to LCs generated from umbilical cord blood CD34+ progenitor cells to identify LC-specific genes and the expression of these genes in LCH was investigated. Besides the expression of several genes known to be highly expressed in LCs and LCH such as CD1a, LYZ, and CD207, high expression of genes not previously reported to be expressed in LCs, such as GSN, MMP12, CCL17, and CCL22, was also identified. Further analysis of these genes by quantitative RT-PCR revealed high expression of FSCN1 and GSN in all 12 LCH cases analysed; of CD207, MMP12, CCL22, and CD1a in the majority of these cases; and CCL17 in three of the 12 cases. Immunohistochemistry confirmed protein expression in the majority of cases. The expression of MMP12 was most abundant in multi-system LCH, which is the LCH type with the worst prognosis. This suggests that expression of MMP12 may play a role in the progression of LCH. These data reveal new insight into the pathology of LCH and provide new starting points for further investigation of this clonal proliferative disorder.

Keywords

Actin, Actin binding protein gelsolin, Actin bundling protein fascin, CCL17, CCL22, CD1a, CD207, CFL1, CST3, Chemokine CCL17, Chemokine CCL22, DC-100-CRY, Dendritic cells, FSCN1, FTL, Fascin, GSN, Gene expression, IFT30, LGALS1, LYZ, Langerhans cell histiocytosis (LCH), Langerhans cells, MMP, MMP12, Metalloproteinase MMP12, RAB5C, S100A10, SIAT6, Serial analysis of gene expression (SAGE), ZNF216, ZYK

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